The goal of our research is to understand how the carbohydrate attached to glycoproteins influences their function and metabolism. Our first objective is to be determine how the oligosaccharides on IgM and galactose residues on IgG mediate immune clearance of soluble IGM- or IgG-antigen complexes from the circulation. We now wish to investigate the molecular mechanisms by which carbohydrate dependent immune clearance occurs. We will study how the composition of immune complexes (antigen:antibody ratio) influences (1) exposure of carbohydrate signals (glycosidase releasable carbohydrate) in IgM and IgG, and (2) interaction of complexes with cells involved in the immune response (hepatocytes, macrophages, lymphocytes), and with isolated carbohydrate binding proteins. Through this work we hope to increase our understanding of how circulating immune complexes in immune complex diseases and rheumatoid arthritis escape normal clearance mechanisms. Studies on the role of carbohydrate in the biliary secretion of IgA are also proposed. Our second objective is to determine how enhanced non-enzymatic glucosylation of serum and membrane proteins contributes to the pathophysiology of diabetes. We have recently demonstrated that glucosylation (1) is a common chemical modification of serum proteins, occurring at enhanced rates during diabetic hyperglycemia, and (2) can lead to glucose-dependent chemical crosslinking of proteins. Specific aims are to determine how glucosylation effects the structure and function of plasma proteins (albumin, fibrinogen). We will also examine the extent of glucosylation and crosslinking of serum and cell membrane proteins in normal and diabetic rats. These studies will expand our knowledge of the metabolic sequelae of hyperglycemia, and may suggest new routes for therapeutic mangement of diabetes.